ABSTRACT
Colorectal cancer (CRC) is the third most prevalent cancer with the second-highest mortality rate worldwide. microRNAs (miRNAs) of cancer-derived exosomes have shown promising diagnosis potential. Recent studies have shown the metastatic potential of a specific group of microRNAs called metastasis. Therefore, down-regulation of miRNAs at the transcriptional level can reduce metastasis probability. The aim of this bioinformatics research is targeting of miRNAs precursors using CRISPR-C2c2 (Cas13a) technique. The C2c2 (Cas13a) enzyme structure was downloaded from the RCSB database, the sequence miRNAs and their precursors were collected from miRbase. The crRNAs were designed and evaluated for their specificity by using CRISPR-RT server. The modeling 3D structure of the designed crRNA was performed by RNAComposer server. Finally, HDOCK server was used to perform molecular docking to evaluate docked molecules' energy level and position. The crRNAs designed for miR-1280, miR-206, miR-195, miR- 371a, miR-34a, miR-27a, miR-224, miR-99b, miR-877, miR-495 and miR-384 that showed high structural similarity with the situation observed in normal and appropriate orientation was obtained. Despite high specificity, the correct orientation was not established in the case of crRNAs that designed to target miR-145, miR-378a, miR-199a, miR- 320a and miR-543. The predicted interactions between crRNAs and Cas13a enzyme showed that crRNAs have a strong potential to inhibit metastasis. Therefore, crRNAs may be considered as an effective anticancer agent for further research in drug development.
ABSTRACT
Contamination of soil with chromium (Cr) is a rising problem in terms of agricultural sustainability and food safety. Here, the effects of methyl jasmonate (MJ; 0, 5, and 10 µM) on alleviating Cr stress (0, 100, and 200 µM) were surveyed in pot marigold (Calendula officinalis L.). The results showed that Cr stress significantly reduced photosynthetic pigments and leaf accumulation of total soluble sugars, total starch, and mineral nutrients and, consequently, lowered the height and biomass of pot marigold plants. Chromium toxicity also increased the leaf levels of oxidative stress markers and induced oxidative stress, which was associated with damage to bio-membranes and increased levels of malondialdehyde. However, MJ supplementation reduced the leaf accumulation of Cr, increased the content of photosynthetic pigments, and improved the performance of the photosynthetic machinery in Cr-stressed plants. MJ supplementation boosted the antioxidant defense system by upregulating antioxidant enzymes, glyoxalase enzymes, and the ascorbate-glutathione (AsA-GSH) pool redox, which significantly diminished Cr-induced oxidative stress. Hence, MJ supplementation might be a practicable approach for reducing Cr absorption and its negative impacts on pot marigold plants growing under Cr-contaminated conditions. Clinical trials registration Not applicable.
